MIT-E: A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy

Sponsor

PTC Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04378075

Collaborator

(none)

Enrollment

Locations

Arms

33.6

Anticipated Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a parallel-arm, double-blind, placebo-controlled study with a screening phase that includes a 28-day run-in phase to establish baseline seizure frequency, followed by a 24-week, randomized, placebo-controlled phase. After completion of the randomized, placebo-controlled phase, participants may enter a 48-week, long-term, extension phase during which they will receive open-label treatment with vatiquinone.

Condition or Disease	Intervention/Treatment	Phase
Mitochondrial Diseases Drug Resistant Epilepsy Leigh Disease Leigh Syndrome Mitochondrial Encephalopathy (MELAS) Pontocerebellar Hypoplasia Type 6 (PCH6) Alpers Disease Alpers Syndrome	Drug: Vatiquinone Other: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease Subjects With Refractory Epilepsy

Actual Study Start Date :

Sep 28, 2020

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Jul 19, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vatiquinone 15 milligrams/kilogram (mg/kg) if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, 3 times per day (TID) or up to 72 weeks	Drug: Vatiquinone Vatiquinone will be administered per the treatment arm description. Other Names: PTC743 EPI-743 Other: Placebo Vatiquinone-matching placebo will be administered per the treatment arm description
Placebo Comparator: Placebo Vatiquinone-matching placebo, administered orally, TID for up to 24 weeks followed by vatiquinone 15 mg/kg if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, TID for up to 48 weeks.	Other: Placebo Vatiquinone-matching placebo will be administered per the treatment arm description

Arm

Intervention/Treatment

Experimental: Vatiquinone

15 milligrams/kilogram (mg/kg) if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, 3 times per day (TID) or up to 72 weeks

Drug: Vatiquinone

Vatiquinone will be administered per the treatment arm description.

Other Names:

PTC743

EPI-743

Other: Placebo

Vatiquinone-matching placebo will be administered per the treatment arm description

Placebo Comparator: Placebo

Vatiquinone-matching placebo, administered orally, TID for up to 24 weeks followed by vatiquinone 15 mg/kg if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, TID for up to 48 weeks.

Other: Placebo

Vatiquinone-matching placebo will be administered per the treatment arm description

Outcome Measures

Primary Outcome Measures

Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures per 28 Days [Day 0, Week 24]

Secondary Outcome Measures

Number of Disease-Related Hospital Days [Week 24 and up to Week 72]
Number of Participants with Occurrences or Recurrence of Status Epilepticus [Week 24 and up to Week 72]
Number of Participants with Disease-Related In-Patient Hospitalizations or Emergency Room Visits [Week 24 and up to Week 72]
Number of Disease-Related In-Patient Hospital Admissions or Emergency Room Visits [Week 24 and up to Week 72]
Percent Change From Baseline to Week 72 in Total Seizure Frequency per 28 Days [Day 0, Week 24, Week 72]
Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Motor Seizures [Week 24 and up to Week 72]
Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Total Seizures [Week 24 and up to Week 72]
Number of Participants Who Require Rescue Seizure Medication [Week 24 and up to Week 72]
Health-Related Quality of Life as Measured by the Care-Related Quality of Life of Informal Caregivers (CarerQoL-7D) Questionnaire [Week 24 and up to Week 72]
Number of Participants with Seizure Clusters [Week 24 and up to Week 72]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent form.
Participant or parent/legal guardian is able and willing to complete seizure diaries for the duration of the study.
Genetic confirmation of inherited mitochondrial disease with associated epilepsy phenotype (Alpers/polymerase subunit gamma [POLG], Leigh syndrome, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS]), or other genetically confirmed mitochondrial disease secondary to mitochondrial mutations (Pontocerebellar Hypoplasia Type 6 [PCH6], nuclear DNA RARS2 mutation) or myoclonic epilepsy with ragged red fibers (MERRF, mitochondrial DNA [mtDNA] mitochondrially encoded tRNA lysine [MT-TK] mutation).
Despite ongoing treatment with at least 2 antiepileptic drugs:
have ≥6 observed motor seizures occurring during the 28 days prior to the baseline visit (Day 0).
have ≥2 observed motor seizures in the first 14 days and ≥2 in the second 14 days of the Run-in period (Day -14).
do not have a consecutive 20-day seizure free period.
have at least 80% of seizure diary data.
Documented medical history of epilepsy associated with mitochondrial disease for at least 6 months prior to screening except for participants who are <2 years of age at the time of screening (participants <2 years of age can be considered for enrollment if all other screening criteria are met due to the potential for rapid progression in these participants).
Consent to abstain from non-approved therapies for 30 days prior to the screening visit and for the duration of the study.
Stable dose regimen of antiepileptic therapies 30 days prior to the screening visit.
Stable regimen of dietary supplements 30 days prior and, if on a ketogenic diet, stable ketogenic diet 90 days prior to the screening visit and for duration of the study.
Electroencephalogram (EEG) at screening or historical EEG up to 6 months prior to screening for diagnostic confirmation of seizures.

Exclusion Criteria:

Allergy to vatiquinone or sesame oil.
Aspartate transaminase (AST) or alanine transaminase (ALT) ≥3 × upper level of normal (ULN) at time of screening.
International normalized ratio (INR) >ULN at time of screening.
Serum creatinine ≥1.5 × ULN at time of screening.
Participation in another interventional clinical trial 60 days prior to randomization or for the duration of this clinical trial
Previously received vatiquinone.
Concomitant treatment with drug(s) that have not received regulatory agency approval for the treatment of mitochondrial diseases and use of artisanal (non-Epidiolex cannabidiol) cannabidiol therapies.
Concomitant treatment with idebenone.
Ongoing treatment with strong cytochrome P450 (CYP) inhibitors such as itraconazole or strong CYP inducers such as rifampin. Treatment with these agents must be completed at least 4 weeks prior to enrollment.During the study, participants should not use grapefruit/grapefruit juice or St John's wort extract.
Pregnant or lactating participants or those male or female sexually active participants who are unwilling to comply with proper birth control methods from the time consent is signed until 30 days after treatment discontinuation. Females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit (Day 0).
Comorbidities that may confound study results (for example, fat malabsorption syndrome, other mitochondrial disorders) in the opinion of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California	San Diego	California	United States	92123
2	Stanford University	Stanford	California	United States	94305
3	Yale School of Medicine	New Haven	Connecticut	United States	06520
4	Children's National Medical Center - Department Of Neurology	Washington	District of Columbia	United States	20010
5	John Hopkins Medicine	Baltimore	Maryland	United States	21287
6	Pediatric Genetics Clinic (Main MGH Hospital)	Boston	Massachusetts	United States	02114-2696
7	Boston Children Hospital	Boston	Massachusetts	United States	02115
8	Children's of Minnesota	Minneapolis	Minnesota	United States	55404
9	Akron Children's Hospital	Akron	Ohio	United States	44308
10	Baylor College of Medicine	Houston	Texas	United States	77030
11	University of Texas Health Science	Houston	Texas	United States	77030
12	Seattle Children's hospital	Seattle	Washington	United States	98105
13	Alberta Children's Hospital, University of Calgary	Calgary		Canada	T3B 6A8
14	CHU d'Angers - Service de génétique	Angers		France	49933
15	CHU de Montpellier - Hôpital Gui de Chauliac - Département de neuropédiatrie	Montpellier		France	34295
16	A.P.H.P - Hôpital Necker-Enfants Malades - Service de Neurologie pédiatrique	Paris		France	75015
17	CHU de Strasbourg - Hôpital de Hautepierre - Service de Neuropédiatrie	Strasbourg		France	67200
18	UOC Neuropsichiatria Infantile, Istituto Neurologico Carlo Besta-Fondazione IRCCS	Milano		Italy	20133
19	U.O.C. Malattie Muscolari e Neurodegenerative, Dipartimento di Scienze Neurologiche e Psichiatriche, Ospedale Pediatrico Bambino Gesù	Roma		Italy	00165
20	Chiba Children's Hospital	Chiba		Japan	266-0007
21	Hokkaido University Hospital	Sapporo		Japan	060-8648
22	Hospital Sant Joan de Déu	Barcelona		Spain	08950
23	Hospital Ruber Internacional, Neurology Department, Epilepsy Program	Madrid		Spain	28034
24	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
25	Great Ormond Street Hospital for Children NHS Foundation Trust	London		United Kingdom	WC1N 3JH
26	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne		United Kingdom	NE1 4LP